Overexpression of SmeGH contributes to the acquired MDR of Stenotrophomonas maltophilia

Li Hua Li, Man San Zhang, Chao Jung Wu, Yi Tsung Lin, Tsuey Ching Yang

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Background: Stenotrophomonas maltophilia displays high-level resistance to various antibiotics. Fluoroquinolone is among the few treatment options for S. maltophilia infection. Overexpression of SmeDEF, SmeVWX and SmQnr are the main mechanisms responsible for fluoroquinolone resistance in S. maltophilia. Objectives: To reveal the unidentified fluoroquinolone resistance mechanisms in S. maltophilia. Methods: Fluoroquinolone-resistant spontaneous mutants were selected by spreading KJDDEFD5, a SmeDEF- and SmeVWX-null double mutant, on ciprofloxacin- or levofloxacin-containing medium. Antibiotic susceptibility was assessed by the agar dilution method. Outer membrane protein profiles of fluoroquinolone-resistant mutants were assayed by SDS-PAGE and significant protein was characterized by LC-MS/MS. The expression of tolCsm, smeH, smeK, smeN, smeP, smeZ and smQnr was investigated by real-time quantitative PCR. The contribution of SmeGH overexpression to antibiotic resistance was verified by DsmeH mutant construction and smeGH complementation assay. Results: Most fluoroquinolone-resistant mutants displayed MDR. The TolCsm protein and smeH transcript were concomitantly overexpressed in some MDR mutants. smeH deletion increased the susceptibility of the MDR mutants to fluoroquinolone, macrolide, chloramphenicol and tetracycline, and the resistance compromise was partially reversed by complementation with a plasmid containing smeGH. SmeGH overexpression was found in some fluoroquinolone-resistant clinical S. maltophilia isolates whose SmeDEF, SmeVWX and SmQnr proteins were not or were lowly expressed. Conclusions: Overexpression of SmeGH contributes to the acquired resistance of S. maltophilia to fluoroquinolone, macrolide, chloramphenicol and tetracycline.

Original languageEnglish
Pages (from-to)2225-2229
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume74
Issue number8
DOIs
Publication statusPublished - Aug 2019
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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